| Abstract: | Many drugs exhibit altered pharmacokinetic parameters in burn patients. We prospectively evaluated the pharmacokinetics of ciprofloxacin in eight burn patients with active infections. Each patient received a 400-mg dose of ciprofloxacin intravenously (i.v.) every 8 h, with each dose infused over 1 h by using a rate control device. Blood samples for analysis of plasma ciprofloxacin concentrations, determined by high-performance liquid chromatography, were obtained immediately predose, at the end of the infusion, and 1, 2, 3, 4, 5, 6, and 7 h after the end of the infusion. Urine was collected from 0 to 2, 2 to 4, and 4 to 8 h following the same dose, and an aliquot was saved for determination of the ciprofloxacin concentration. Urine was also collected for 24 h prior to this dose for measurement of creatinine clearance (CLCR). Pharmacokinetic parameters were estimated by noncompartmental analysis. Mean maximum and minimum plasma ciprofloxacin concentrations were 4.2 +/- 1.1 and 0.70 +/- 0.55 microgram/ml, respectively. Mean values for clearance (CL), renal clearance (CLR), volume of distribution, terminal elimination rate constant, half-life (t1/2), and area under the concentration-time curve (AUC) were 29.1 +/- 17.5 liters/h, 13.5 +/- 10.1 liters/h, 1.75 +/- 0.41 liters/kg, 0.222 +/- 0.098 h-1, 4.5 +/- 3.9 h, and 20.7 +/- 16.6 micrograms.h/ml, respectively. CL was higher and t1/2 was shorter than noted in previous studies of acutely ill, hospitalized patients. A good correlation was noted between creatinine clearance CL(CR) and both total ciprofloxacin CL (r = 0.85) and CLR (r = 0.84). A moderate inverse correlation was noted between percent body surface area burned and total ciprofloxacin CL (r = -0.55). An AUC/MIC ratio above 125 SIT-1 (where SIT is serum inhibitory titer), which has been strongly correlated with clinical response and time to bacterial eradication, was achieved in five of eight patients (63%) with a MIC of 0.25 microgram/ml. At a ciprofloxacin dosage of 400 mg i.v. every 12 h, an AUC/MIC ratio above 125 SIT-1 would have been achieved in only two of eight patients (25%). We conclude that ciprofloxacin CL is highly variable, but generally increased, in burn patients compared with that in acutely ill, general medical and surgical patients. Because of an increase in CL, a ciprofloxacin dosage of 400 mg i.v. every 8 h is more likely to produce the desired response in burn patients than the same dose given every 12 h. |
